Karen S. Servilla

Which Targets in Clinical Practice Guidelines Are Associated with Improved Survival in a Large Dialysis Organization

Professional organizations have developed practice guidelines in the hope of improving clinical outcomes. The National Kidney Foundations Kidney Disease Outcomes Quality Initiative (KDOQI) has set targets for dialysis dosage (single-pool Kt/V), hematocrit, serum albumin, calcium, phosphorus, parathyroid hormone, and BP for hemodialysis (HD) patients. Several guidelines are largely based on results from observational studies. In contrast to other parameters, BP values within the KDOQI guidelines have been associated with increased mortality. Therefore, it was postulated that having multiple parameters that satisfy the current guidelines, except those for BP, is associated with improved survival among HD patients. A retrospective analysis was conducted of incident HD patients who were treated at facilities operated by Dialysis Clinic Inc., a not-for-profit dialysis provider, between January 1, 1998, and December 31, 2004 (n = 13,792). Cox proportional hazards models were used to assess the association between satisfying guidelines and mortality. Values within guidelines for single-pool Kt/V, hematocrit, serum albumin, calcium, phosphorus, and parathyroid hormone were associated with decreased mortality (P < or = 0.0001). The largest survival benefit was found for serum albumin (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.24 to 0.31). Satisfying these six guidelines simultaneously was associated with an 89% reduction in mortality (HR 0.11; 95% CI 0.06 to 0.19]). Conversely, BP values satisfying the guideline were associated with increased mortality (HR 1.90; 95% CI 1.73 to 2.10). Because this target was largely extrapolated from the general population, a randomized, controlled trial is needed to identify the optimal BP for HD patients.

Age, Race, Diabetes, Blood Pressure, and Mortality among Hemodialysis Patients

Observational studies involving hemodialysis patients suggest a U-shaped relationship between BP and mortality, but the majority of these studies followed large, heterogeneous cohorts. To examine whether age, race, and diabetes status affect the association between systolic BP (SBP; predialysis) and mortality, we studied a cohort of 16,283 incident hemodialysis patients. We constructed a series of multivariate proportional hazards models, adding age and BP to the analyses as cubic polynomial splines to model potential nonlinear relationships with mortality. Overall, low SBP associated with increased mortality, and the association was more pronounced among older patients and those with diabetes. Higher SBP associated with increased mortality among younger patients, regardless of race or diabetes status. We observed a survival advantage for black patients primarily among older patients. Diabetes associated with increased mortality mainly among older patients with low BP. In conclusion, the design of randomized clinical trials to identify optimal BP targets for patients with ESRD should take age and diabetes status into consideration.

Effects of Intensive BP Control in CKD

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

Anemia Management and Association of Race With Mortality and Hospitalization in a Large Not-for-Profit Dialysis Organization

BACKGROUND The optimal hemoglobin target and possible toxicity of epoetin therapy in hemodialysis patients are controversial. Previous studies suggest that African American patients use higher doses of epoetin and have better survival compared with white hemodialysis patients. STUDY DESIGN Retrospective longitudinal cohort. SETTING & PARTICIPANTS Epoetin-exposed incident hemodialysis patients (N = 12,733; African Americans, n = 4,801; white, n = 7,386) treated in Dialysis Clinic Inc facilities during 2000 to 2006. PREDICTORS Hemoglobin, epoetin, iron. OUTCOMES Mortality, hospitalization. MEASUREMENTS Proportional hazards models with time-varying covariates. RESULTS Hemoglobin concentrations less than 10 g/dL in whites and less than 11 g/dL in African Americans were associated with increased mortality and hospitalization versus the referent hemoglobin level of 11 to 11.9 g/dL. Hemoglobin levels of 13 g/dL or greater in whites were associated with decreased noncardiovascular mortality. Six-month cumulative epoetin doses of 20,000 U/wk or greater were associated with increased mortality and hospitalization versus the referent group (8,000 to 12,499 U/wk). Epoetin doses less than 8,000 U/wk were associated with decreased risk. Higher epoetin doses were associated with increased mortality at hemoglobin concentrations of 10 to 12.9 g/dL and with increased hospitalization at all hemoglobin concentrations of 10 g/dL or greater. Higher epoetin doses were associated with increased mortality and hospitalization within each tertile of serum albumin concentration. These patterns did not differ by race. LIMITATIONS Treatment-by-indication bias and unidentified confounders cannot be excluded. Small sample sizes in the highest and lowest hemoglobin strata decrease statistical power. CONCLUSIONS Relationships between hemoglobin concentration and mortality differed between African Americans and whites. Additionally, the relationship of lower mortality with greater achieved hemoglobin concentration seen in white patients was observed for all-cause, but not cardiovascular, mortality. A higher cumulative epoetin dose was associated with worse outcomes, even in patients with albumin levels greater than 4 g/dL. There were no statistically significant interactions between race and epoetin dose. Further studies are needed to confirm and to define the mechanism of these findings.

Computerized Decision Support for EPO Dosing in Hemodialysis Patients

BACKGROUND Anemia management in hemodialysis patients poses significant challenges. The present study explored the hypothesis that computerized dosing of intravenous erythropoietin (EPO) would increase the percentage of hemoglobin (Hb) values within the target range and reduce staff time spent on anemia management. STUDY DESIGN Retrospective cohort. SETTING & PARTICIPANTS In-center hemodialysis patients who received EPO at Dialysis Clinic Inc dialysis units for at least 3 months between October 1, 2005, and April 30, 2006. QUALITY IMPROVEMENT PLAN Computerized decision support (CDS) for EPO dosing is compared with manual physician-directed dosing. OUTCOMES Achieved monthly Hb values, quantity of EPO administered, and time spent by dialysis unit personnel. MEASUREMENTS Monthly Hb and quantity of EPO administered to 1,118 patients from 18 dialysis units treated using CDS and 7,823 patients from 125 dialysis units treated using manual dosing. RESULTS There was no difference in the likelihood of a monthly Hb level of 11-12 or 10-12 g/dL using CDS compared with manual dosing. The likelihood of an Hb level > 12 g/dL decreased and the likelihood of an Hb level < 10 g/dL increased using CDS. EPO use was 4% lower using CDS, although the difference was not statistically significant. CDS was associated with a nearly 50% decrease (P < 0.001) in the time spent by dialysis unit staff on anemia management. LIMITATIONS Retrospective and nonrandomized. CONCLUSION The number of monthly Hb values in an 11- (and 10-) to 12-g/dL target range and EPO use did not differ with EPO dosing using CDS compared with manual dosing. Staff resources devoted to anemia management decreased significantly using CDS.

Increased CD36 Expression Signals Monocyte Activation Among Patients With Type 2 Diabetes

OBJECTIVE To explore the hypothesis that CD36, a scavenger receptor and fatty acid translocase, is upregulated in peripheral blood mononuclear cells (PBMCs) among patients with type 2 diabetes and is a biomarker of PBMC activation and inflammation. RESEARCH DESIGN AND METHODS We used a cross-sectional observational design to study a multi-racial/ethnic population sample consisting of Caucasians, Hispanics, and Native Americans with type 2 diabetes (n = 33) and nondiabetic control subjects (n = 27). PBMC CD36 mRNA/protein and plasma high sensitivity (hs) C-reactive protein (hsCRP), hs–interleukin-6 (hsIL-6), and adiponectin were measured. RESULTS Unadjusted PBMC CD36 mRNA and protein were 1.56- and 1.63-fold higher, respectively, among type 2 diabetic subjects versus control subjects. PBMC CD36 protein was directly associated with CD36 mRNA, plasma hsCRP, and hsIL-6 and inversely associated with plasma adiponectin in both groups. CONCLUSIONS Increased CD36 expression is a biomarker of PBMC activation and inflammation and may become a useful tool in cardiovascular disease risk stratification.

Effects of intensive systolic blood pressure control on kidney and cardiovascular outcomes in persons without kidney disease

Background The public health significance of the reported higher incidence of chronic kidney disease (CKD) with intensive systolic blood pressure (SBP) lowering is unclear. Objective To examine the effects of intensive SBP lowering on kidney and cardiovascular outcomes and contrast its apparent beneficial and adverse effects. Design Subgroup analyses of SPRINT (Systolic Blood Pressure Intervention Trial). (ClinicalTrials.gov: NCT01206062). Setting Adults with high blood pressure and elevated cardiovascular risk. Participants 6662 participants with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2. Intervention Random assignment to an intensive or standard SBP goal (120 or 140 mm Hg, respectively). Measurements Differences in mean eGFR during follow-up (estimated with a linear mixed-effects model), prespecified incident CKD (defined as a >30% decrease in eGFR to a value <60 mL/min/1.73 m2), and a composite of all-cause death or cardiovascular event, with surveillance every 3 months. Results The difference in adjusted mean eGFR between the intensive and standard groups was -3.32 mL/min/1.73 m2 (95% CI, -3.90 to -2.74 mL/min/1.73 m2) at 6 months, was -4.50 mL/min/1.73 m2 (CI, -5.16 to -3.85 mL/min/1.73 m2) at 18 months, and remained relatively stable thereafter. An incident CKD event occurred in 3.7% of participants in the intensive group and 1.0% in the standard group at 3-year follow-up, with a hazard ratio of 3.54 (CI, 2.50 to 5.02). The corresponding percentages for the composite of death or cardiovascular event were 4.9% and 7.1% at 3-year follow-up, with a hazard ratio of 0.71 (CI, 0.59 to 0.86). Limitation Long-term data were lacking. Conclusion Intensive SBP lowering increased risk for incident CKD events, but this was outweighed by cardiovascular and all-cause mortality benefits. Primary Funding Source National Institutes of Health.

Pyocystis in patients on chronic dialysis. A potentially misdiagnosed syndrome

Pyocystis is an important complication of non-functioning urinary bladder, which often poses diagnostic difficulties. We present a case of pyocystis in a patient on chronic hemodialysis who was anuric for one year. The patient was initially diagnosed with diverticulitis. An abdominal C-T scan suggested the diagnosis of pyocystis, which was confirmed by bladder catheterization. The patient was treated with bladder drainage and a prolonged antibiotic course, followed by intermittent saline washing of the bladder.

Death during hospitalization in patients on chronic hemodialysis

Mortality from various causes is higher in patients on chronic hemodialysis (HD) than in the general population. There is evidence suggesting that some of the deaths in HD patients are preventable. To identify potentially preventable causes of death, we analyzed deaths that occurred in HD patients during hospitalization over a period of 15 years. We performed a retrospective cohort analysis of 410 patients on HD for at least 6 months between 1995 and 2009 (included), who had all their hospitalizations in the same hospital. The patients were classified into 3 groups: Those who died during hospitalization (group A, n=120), those who died away from the hospital (group B, n=135), and those who were alive at the end of the observation period (group C, n=155). Continuous variables were compared between groups by the Kruskall‐Wallis statistic. Logistic regression was used to identify predictors of dying during the observation period and predictors of death in the hospital. For the whole HD group of 410 patients, only 9 (2.2%) were women. 59% of the patients had diabetes mellitus. Age at the onset of HD was 65.8 ± 11.5 years and the duration of HD was 34.4 ± 27.9 months. Group A patients had a higher annual rate and duration of hospitalization and a higher Charlson comorbidity index than either of the other 2 groups, and, in comparison with patients in group C, were older at the end of observation and had a shorter duration of HD. Cardiac disease (19.2%), vascular access complications (18.3%), peripheral vascular disease (16.7%), infections (15.8%), trauma (11.7%), central nervous system disease (7.5%), respiratory failure (4.2%), malignancy (3.3%), and gastrointestinal disease (3.3%) were the causes of the last hospitalization in group A. Compared with the patients who died during hospitalization without discontinuing HD, group A patients who discontinued HD had a longer duration of their last hospitalization (52.7 ± 77.7 vs. 14.3 ± 23.8 days, P<0.001). Discontinuation of HD occurred in 80% of the hospitalizations for respiratory failure, 75% of the hospitalizations for malignancy, 57% of the hospitalizations for trauma, and 56% of the hospitalizations for central nervous system disease. Logistic regression identified a high Charlson index, advanced age, and short duration of HD as predictors of death, and an absence of diabetes, high Charlson index, prolonged annual duration of hospitalization, and short distance of the patients domicile from the dialysis unit as predictors of death in the hospital. A substantial number of hospitalizations leading to the death of HD patients are caused by potentially preventable conditions, including vascular access complications, peripheral vascular disease, and trauma. Implementation of measures preventing these hospitalizations is a worthwhile undertaking.

Hospitalizations before and after initiation of chronic hemodialysis

Hospitalization rate is high in patients on chronic hemodialysis (HD). We investigated whether initiation of HD changes the rate and length of hospitalization. We analyzed hospitalizations in HD patients in one hospital over 15 years. We compared annual rate and length of hospitalizations, both presented as mean (95% confidence interval [CI]) between the pre‐HD and HD period. Three hundred ninety‐two patients, 98% men, 59% diabetic, and 66.3 ± 11.2 years old at the onset of HD, had 1016 hospitalizations in the pre‐HD period (60.0 ± 42.9 months) and 1627 hospitalizations in the HD period (32.5 ± 25.9 months). Higher values were found in the HD than the pre‐HD period for rate, (pre‐HD 0.557 [95% CI 0.473–0.611], HD 2.198 [95% CI 1.997–2.399] admissions/[patient‐year], P<0.001) and length (pre‐HD 4.63 [95% CI 3.71–5.55], HD 28.07 [95% CI 23.55–32.59] days/patient‐year], P<0.001) of hospitalizations for all causes, cardiac disease, infections, vascular access, peripheral vascular disease, metabolic disturbances, gastrointestinal diseases, and miscellaneous conditions, mainly respiratory illness and malignancy. Similar differences were found when we compared the year before and the year after the start of HD. Diabetics had higher all cause rate and length of hospitalizations than non‐diabetics in the pre‐HD and HD periods. The rate and length of hospitalizations was higher in the HD than the pre‐HD period for both HD‐specific conditions and conditions encountered in both HD and general populations. Study of factors specific to HD that may affect these conditions should constitute the first step toward improving the morbidity of patients on HD.